Arterial hypertension is one of the most important risk factors for cardiovascular morbidity and mortality. Recent epidemiological analyses show that the prevalence of arterial hypertension increases dramatically in Germany and also world-wide. The clinical importance of arterial hypertension is associated with resulting in cardiovascular end-organ damages. About 90-95% of the patients suffering from hypertension have a so called “primary hypertension”, which refers to high blood pressure for which no medical cause can be found (Carretero O A, Oparil S (January 2000), “Essential hypertension. Part I: definition and etiology”, Circulation 101 (3): 329-35). In the remaining 5-10% of the cases hypertension is caused by other conditions that affect kidneys, arteries, heart, or the endocrine system. These patients suffer from a so called “secondary hypertension” (Pierdomenico S D, Di Nicola M, Esposito A L, et al. (June 2009), “Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients”, American Journal of Hypertension 22 (8): 842-7).
Regularly, hypertension is diagnosed on the basis of a persistently high blood pressure. Initial assessment of the hypertensive patient should include a complete history and physical examination. If the elevation is extreme or if symptoms of organ damage are present, treatment has to start immediately to prevent further damages.
After the diagnosis of hypertension, physicians will attempt to identify the underlying cause based on risk factors and other symptoms. Secondary hypertension, i.e. hypertension caused by other conditions is more common in preadolescent children. In most cases it is caused by a renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Laboratory tests can also be performed to identify possible causes of secondary hypertension and determine if hypertension has caused damage to the heart, eyes, and kidneys.
Pre-eclampsia is a syndrome of hypertension, oedema, and proteinuria that affects 5 to 10% of pregnancies and results in substantial maternal and fetal morbidity and mortality. Pre-eclampsia accounts for at least 200,000 maternal deaths worldwide per year. The symptoms of pre-eclampsia typically appear after the 20th week of pregnancy and are usually detected by routine monitoring of the woman's blood pressure and urine. However, these monitoring methods are ineffective for diagnosis of the syndrome at an early stage. Such early detection could reduce the risk for the subject or developing fetus, if an effective treatment were available. Currently there are no known cures for pre-eclampsia. Pre-eclampsia can vary in severity from mild to life-threatening. A mild form of pre-eclampsia can be treated with bed rest and frequent monitoring. For moderate to severe cases, hospitalization is required and blood pressure medication or anticonvulsant medications to prevent seizures are administered. If the condition becomes life-threatening to the mother or the baby the pregnancy is terminated and the baby is delivered pre-term.
Fifteen years ago, a panel of experts representing the full spectrum of cardiovascular disease (CVD) research and practice assembled at a workshop to examine the state of knowledge about CVD. The leaders of the workshop generated a hypothesis that framed CVD as a chain of events, initiated by a myriad of related and unrelated risk factors and progressing through numerous physiological pathways and processes to the development of end-stage heart disease; see FIG. 10 They further hypothesized that intervention anywhere along the chain of events leading to CVD could disrupt the pathophysiological process and confer cardioprotection. The workshop participants endorsed this paradigm but also identified the unresolved issues relating to the concept of a CVD continuum. There was limited availability of clinical trial data and pathobiological evidence at that time, and the experts recognized that critical studies at both the mechanistic level and the clinical level were needed to validate the concept of a chain of events leading to end-stage CVD.
In the intervening 15 years, new evidence for underlying pathophysiological mechanisms, the development of novel therapeutic agents, and the release of additional landmark clinical trial data have confirmed the concept of a CVD continuum and reinforced the notion that intervention at any point along this chain can modify CVD progression. In addition, the accumulated evidence indicates that the events leading to disease progression overlap and intertwine and do not always occur as a sequence of discrete, tandem incidents. Furthermore, although the original concept focused on risk factors for coronary artery disease (CAD) and its sequelae, the CVD continuum has expanded to include other areas such as cerebrovascular disease, peripheral vascular disease, and renal disease. Since its conception 15 years ago, the CVD continuum has become much in need of an update.
The recently described prorenin receptor (PRR) is a new trans-membrane receptor that binds both renin and prorenin. This binding increases the catalytic activity of renin four to five fold, activates prorenin nonproteolytically and induces the activation of MAP-kinase ERK½. The extracellular part is cleaved after amino acid 277. However, its function has not been fully understood yet.
However, so far, all known tests are restricted to one or few caused cardiovascular end-organ damages or conditions causing hypertension. Thus, there is a need for a reliable method to diagnose hypertension and/or cardiovascular end-organ damage. The problem underlying the present invention, therefore, may in one aspect be seen in the provision of a method for the diagnosis of hypertension and/or cardiovascular end-organ damage.
The inventors have unexpectedly found that the presence of soluble PRR (sPRR; SEQ ID NO. 2) in samples of subjects are indicative for the presence of hypertension and/or cardiovascular end-organ damage as well other disease states of the CVD continuum.
So far it was not possible to detect sPRR in samples of subjects using standard ELISA. The inventors now unexpectedly found that an antibodies specifically binding to the amino acid sequence of SEQ ID NO. 4 are well suited for the detection of sPRR in samples of subjects. By that the inventors provide an antibody which allows the detection of sPRR and contributes to the solution of the above mentioned problems.